Keto-quaternary compounds

ABSTRACT

Novel keto-quaternary ammonium compounds which include the adamantane ring system linked to the quaternary ammonium group by a keto group.

United States Patent Bauman Sept. 23, 1975 KETO-QUATERNARY COMPOUNDS [56] References Cited [75] Inventor: Robert Andrew Bauman, New UNITED STATES PATENTS Brunswick, 3,565,942 2/1971 Krimmel 260/468 G 3,591,642 v7/1971 Szinai et al. [73] Asslgnee' gg f g New 3,663,617 511972 Pedrazzoli et al 260/563 P I ER P BLI A [22] Filed: Feb. 25, 1974 GT U TIONS Stepanov et aI.,- Zh. Organ. Khlm 2(4), pp. 644-648.

[21] Appl. No.: 445,542

Related U.S. Application Data Continuation-in-part of Ser. No. 400,097, Sept. 24, 1973, which is a continuation of Ser. No. 39,536, May 21, 1970, abandoned.

U.S. Cl 260/567.6 M; 424/329; 424/54;

260/501.15; 260/459 Int. Cl. C07c 87/00 Field of Search 260/567.6 M, 468 G, 584 R,

[57] ABSTRACT Novel keto-quaternary ammonium compounds which include the adamantane ring system linked to the quaternary ammonium group by a keto group.

4 Claims, No Drawings I KETO-QUATERNARY COMPOUNDS The present application is a continuation-in-part of copending application Ser. No. 400.097 filed Sept. 24. 1973, which is a continuation of patent application Ser. No. 39. 536 filed May 21. l970.'now abandoned.

The present invention relates to novel quaternary ammoniumcompounds represented by the general formula:

whereinR is l-am adantyl '(C Hi R is a long chain alkyl group of l l 8 carbon atoms, 11 is an integer from 1 to 3 and X is a compatible anion such as the halides (Cl' Br, I), sulfates (i.e.. methyl sulfateynitrate. aryl sulfonates, etc. The quaternary compounds possess superior anti-microbial. anti-caries and anti-calculus activity.

The adamantyl radical is derived from tricyclo- [3.3. l l ldeeane showing four fused chair cyelohexane rings as follows:

Typical examples of the quaternary ammonium compounds which may be used in this invention are: 2adamantylearbonylethyldimethyldeeylammonium bromide. 3-adamantylcarbonylpropyldimethyltetradecylammonium bromide, Z-adamantylcarbonylethyldimethylhexadecylammonium bromide, l-adamantylearbonylethyldimethyloctadeeylammonium bromide, l-adamantylcarbonylmethyldimethyltetradecylammonium bromide, l-adamantylcarbonylmethyldimethyldodecylammonium bromide. Other halides such as the chlorides, iodides and analogous compounds such as the sulfates, nitrate, aryl sulfonates, ctc.. may also be employed herein as effective anti-bactericides.

It has been observed that the compounds generally described by the foregoing formula are particularly effective against gram positive organisms such as Staphylococcus our-cur. Streptococcus mitis, Bacillus .s'ubti lis. Coryncbacterium acnes. and against fungi. such as Candida albicans, 'I'riclzop/zyrrm menlogrophytes and Aspergillus niger. and moderately effective against Ext-heric/n'a coli which is a gram negative bacterium. Compounds wherein R is a benzyl radical in lieu of instant higher alkyl radical would be devoid of anti-bacterial activity.

The anti-microbial nature of the instant novel compounds was shown by a standard test tube serial dilution test in which an appropriate number of test tubes of broth containing decreasing concentrations of the test agent was inoculated with the test organism. After a suitable period of incubation the tubes were examined for the presence or absence of growth. The activity of the test agent was the lowest concentration which inhibited the growth of the organism and 'is expressed as the minimal inhibitory concentration in ug/ml.

In general. smaller concentrations of the subject compounds are required to inhibit the growth of the organisms than of analogous compounds which contain substantially the'same number of carbon atoms.

When used against bacteria or fungi. compounds of the instant invention may he applied directly to the surface to be protected or may be dissolved in a pharmaceutical carrier.'Typically. an effective amount, e.g. 0.] to about-10% by weight ofthe' eompound.-is included in an inert carrier and a dispersing or. surface active agent. Alternatively. an effective amount. eg 0.] to about' l0 /z by weight may be incorporated into a solid carrier which may be inert. such as talc. clay. diatomaceous earth. flour. etc.

When compounds of the instant invention are intended for use in compositions which reduce formation of caries and inhibit formation of oral calculus. they are typically incorporated in oral preparations in effective amounts up to about 5% by weight. preferably .025] '7! and most'preferably 0.050.5'/1'by weight of the oral preparation. Typically. the oral preparation is a dentrifrice. such as a dental cream. tablet or powder. containing as a vehicle about 20-95% by weight of a waterinsoluble polishing material. preferably including water-insoluble phosphate such as dicalcium phosphate, tricalcium phosphate. trimagnesium phosphate. The dentrifrice may also include water; binders such as glyeerine. sorbitol, propylene glycol. and polyethylene glycol 400; detergents; gelling agents such as Irish moss and sodium carboxymethyl cellulose; additional antibacterial agents. coloring or whitening agents; preservatives; silieones; chlorophyll compounds; additional ammoniated materials; flavoring or sweetening materials; and compounds which provide fluorine-containing ion such as sodium flouride, stannous flouride and sodium monofluorophosphate.

The oral preparation may also be a liquid such as mouth rinse which typically contains 20-997! by weight of an aqueous lower aliphatic alcohol, preperably having about 1-3071 by weight alcohol, such as ethanol. n-propyl. or isopropyl alcohol.

Such oral preparations are typically applied by brushing the teeth or rinsing the oral cavity for 30-90 seconds at least once daily. Typical oral preparations of the invention which can be applied in this manner are set forth below.

EXAMPLE 1 Dental Cream Quaternary ammonium 0.50 adamantylkctonc *Nonionic detergent L00 Glycerine 22.00 Sodium pyrophosphate 0.25 Carboxymethyl cellulose 0.85 Sodium saccharin 0.20 Sodium henzoate 0.50 Calcium carbonate (precipitated) 5.00 Dicalcium phosphate dihydrate 46.75 Flavor 0.80 Water 2215 *Tween Polyuxyethylene (20 moles ethylene oxide) sorhitan monooleale EXAMPLE 2 !\1oulh Wash Quaternary ammonium 0.05 adamnntylketune *Nonionic detergent (Pluronic F478) 1.00 Ethyl alcohol (containing Flavor) 15.00 Gl 'eerine 10.00 Saceharin 0.02 Water 73.93

EXAMPLE 3 Preparation of l-adamantylcarbonylmethyldimethyltetradecylammonium bromide.

A mixture of 1.3g. (0.005 mole) l-adamantyl bromomethyl ketone and 1.23g. (0.005 mole) dimethyltetradecylamine was solubilized by the addition of cc acetone. The next day the solidified mixture was washed with ether and recrystallized from ethyl acetate to yield 2.1g. white crystals, m.p. l34l35.5C.

Found Calculated Carbon 67.72 (17.45

Hydrogen 10.65 10.5l

EXAMPLE 4 The dodecyl homolog was prepared by the procedure of Example 3 yielding white crystals of melting point l40-l4l.5C and with the following analysis.

Found Calculated Carbon 66.55 (16.36 Hydrogen 9.87 10.18

Although this invention has been described with reference to specific examples. it will be apparent to one skilled in the art that various modifications may be made thereto which will fall within its scope.

What is claimed is: v

1. A chemical compound having the structural formula:

wherein R is l-adamantyl. R is a long chain alkyl group of 10 to 18 carbon atoms, n is an integer from 1 to 3. and X is an anion selected from the group consisting of chloride. bromide, iodide. methyl sulfate. nitrate and arylsulfonates.

2. A chemical compound as set forth in claim 1, wherein X is a halide.

3. l-adamantanecarbonylmethyldimethyldodeeylammonium bromide.

4. l-adamantanecarbonylmethyldimethyltet- 

1. A CHEMICAL COMPOUND HAVING THE STRUCTURAL FORMULA.
 2. A chemical compound as set forth in claim 1, wherein X is a halide.
 3. 1-adamantanecarbonylmethyldimethyldodecylammonium bromide.
 4. 1-adamantanecarbonylmethyldimethyltetradecylammonium bromide. 